Cholesterol: Who needs it?

Uncovering the true lurking killer behind heart disease
By Adam Swenson

The actual relationship between cholesterol and heart disease is complex, a moving target. In his excellent article “The Straight Dope on Cholesterol: 10 Things You Need to Know,” Peter Attia, MD, writes, “One of the unfortunate results of the eternal need to simplify everything is that we, the medical establishment, have done the public a disservice by failing to communicate that there is no such thing as ‘bad’ cholesterol or ‘good’ cholesterol. All cholesterol is imperative for life to exist!

“The only ‘bad’ outcome is when cholesterol ends up inside of the wall of an artery, most famously the inside of a coronary artery or a carotid artery, and leads to an inflammatory cascade which results in the obstruction of that artery.”

Cholesterol 101

Cholesterol is a building block needed for all tissues and cells in the body. Cholesterol is essential to cell structure—it is needed so that cell membranes a) exist at all, and b) have proper permeability and fluidity. It is also a raw material that we need to synthesize steroid hormones (including sex hormones like testosterone and estrogen), bile acids, and corticosteroids which regulate sugar, fat, and protein metabolism and the immune system. Cholesterol is also an essential precursor for the vitamin D produced by sunlight on the skin.

Cholesterol is especially important in peripheral nerves and in the spinal cord and brain. Myelin, an insulating material surrounding nerve cells, is composed primarily of cholesterol—without it signal transmission would be impaired, and neurological mayhem would ensue. (Cholesterol is actually more concentrated in the brain than in any other organ.)

A cholesterol-deprived life is something I wouldn’t wish on anyone. The inability to synthesize cholesterol is a rare genetic disorder known as Smith-Lemli-Opitz syndrome. It is characterized by small head size; intellectual disability; autism; malformation of the heart, lungs, kidneys, GI tract, and genitalia; weak muscle tone; feeding difficulties; and slow growth. Be glad for your cholesterol!

Even the much-maligned LDL cholesterol is vitally important in protecting us against infection. A 1998 study published in Epidemiology and Infection tracked 55,000 men and 65,000 women over a period of 15 years and found that “total cholesterol was inversely and significantly related” to infections in both men and women. People with higher numbers of total cholesterol were less likely to get infections. A University of Pittsburgh study showed that LDL cholesterol protected red blood cells from endotoxin whereas HDL was not protective.

So what’s all the fuss about? If cholesterol is so good (mostly) how did it get such a bad name?

As Peter Attia said earlier, there is one “bad outcome” related to cholesterol—when it lands in the inside of an artery (either coronary or carotid) and leads to inflammation. That can lead to arterial blockage, which anyone who’s watched a couple of Grey’s Anatomy or ER episodes knows is a bad deal. According to the Center for Disease Control and Prevention (CDC,) 600,000 people died of heart disease in 2009, accounting for one in four deaths and making it the leading killer. (For reference, cancer took 567,000 lives, and car accidents 37,000.) Coronary heart disease costs the US $109 billion including health care, medications, and lost productivity. Of course, that also makes heart attacks (and heart attack prevention) big business.

HDL=Ace Disposal, LDL=FedEx

HDL—colloquially known as the “good cholesterol”—means high-density lipoprotein. It helps remove LDL, the “bad cholesterol,” and that’s why it’s regarded as a good thing. HDL takes cholesterol the body is done with and transports it back to the liver, where it is excreted as bile. It is known in cardio-jargon as “nature’s garbage truck,” which isn’t a bad way to think of it.

HDL is much more controlled by genetics than LDL, meaning there’s less you can do to boost your numbers. HDL comes in two varieties, HDL-2 and HDL-3. HDL-2 particles are large, buoyant, and protect against inflammation. HDL-3 are essentially the opposite: small, dense, and potentially inflammatory.

LDL is, in some ways, the converse of HDL. Whereas HDL takes “used-up” cholesterol back to the liver, LDL takes new-off-the-assembly-line cholesterol out to the cells, where it does a great many very important things. If HDL is the garbage truck, LDL is the FedEx man (or woman).

Like HDL, LDL comes in a couple varieties. LDL-A is buoyant and fluffy (much like HDL-2) and not problematic unless damaged by oxidation. LDL-B is small, dense, and a definite problem for atherosclerosis (narrowing/hardening of the arteries).

So your total cholesterol number doesn’t actually tell you a lot about your risk of heart disease. What you really need to know is your LDL-B number, and also your ratio of triglycerides to HDL.

And what discussion of cholesterol would be complete without triglycerides (TG)? TG serve an important function: they are how fat molecules get around in the body. And your TG number is very important, both the overall number and the very important ratio of TG to HDL. That ratio is found by dividing TG by HDL, so if your TG number was 100 and your HDL number was 50, your ratio would be two. That’s a good number—we want this ratio to be low.

This ratio is actually a very good predictor of impending heart disease—far more accurate than total cholesterol. Levels of TG over 120 and HDL at 40 or under (so a ratio of 3 or worse) is a very strong indicator of a predominance of artery-clogging LDL-B. A ratio of three or over is also a very good indicator of insulin resistance. Insulin resistance leads to inflammation, leads to narrower arterial walls and thus higher blood pressure, and increases cholesterol in a way we don’t want.

And what is to blame for knocking this ratio out of whack? Mountain Dew, Twinkies, Slurpies, Ding Dongs, ice cream, cookies … sugar. If someone gives you the choice of a can of full sugar soda and two strips of bacon—go for the bacon every time.

(Lack of exercise, smoking, overconsumption of alcohol, and excess belly fat have a multiplying effect: more on that later.)

Statins: A shotgun approach to a precision problem

Statins are quick and easy and they lower cholesterol. Plus they’re a big moneymaker (to the tune of $30 billion a year), making them a fit for a medical system geared toward quick, easy, expensive answers to things. And, in a way, it’s hard to blame doctors. The alternative is to say “Quit doing all the things that are bad for you (smoking, drinking, sugar) and start doing the things that are good for you (vegetables and walking).”

Who are we kidding? Patients aren’t like that. They want a pill and that’s what they’re getting—an open-and-shut case of “be careful what you wish for.”

In a recent interview with heart expert Joseph Keenan, MD, he said, “It’s just like a reflex for most doctors, if your cholesterol is up a little bit, bam, you go on a statin. I’m being a little judgmental here, but I just know that it’s a lot easier to write a prescription for a statin than to sit and discuss all the lifestyle factors that are important.”

Like most too-easy solutions, statins can have a host of side effects, making one wonder if the cure is, in fact, worse than the disease. In Keenan’s case it certainly was.

“I’m actually a statin casualty,” he said. “I have rather serious muscle problems as a result of taking statins. For instance, my muscle enzyme, the so-called creatine phosphokinase, CPK, is supposed to be around 200. When I was on statins it went up over 800. I felt terrible, muscle aches, cramps, and weak, and didn’t feel like exercising. I just thought, ‘I don’t know what’s wrong with me,’ until I finally got my muscle enzyme checked and I realized I’m destroying my muscles. It was a disaster.”

People take statins to lower cholesterol, but “lowering cholesterol” is not the silver bullet we once thought it was. Edward Pickney, MD, wrote a book titled The Great Cholesterol Conspiracy that tracked twelve studies in which drugs were used to lower cholesterol. Eight of those studies were both randomized and blinded—in six out of eight, deaths were greater in the treatment group than in the control group. For the other four there were no differences in death rate between the control group and the treatment group.

And, if you did want to lower cholesterol, Keenan says, “I know from the various interventions that we’ve done that you can get 30 to 40 percent reduction in cholesterol with a combination of lifestyle and supplements that are not drugs.”

(Here’s another shocker: what you eat doesn’t play as big a role as you thought in total cholesterol. “Just a plain healthy diet probably only gets you about a five percent reduction. It’s funny, your body has a way of adjusting production of things that you limit.” In other words, when you eat less, your body makes more.)

In Jonny Bowden and Stephen Sinatra’s excellent book, The Great Cholesterol Myth, they note that statin drugs are not all bad, just very much overprescribed. Sinatra (MD, FACC) in fact still prescribes low-dose statins “very occasionally to middle-aged men who have already had a heart attack and are at high risk for another.” (But make no mistake, they are very vocal critics of statins.)

So the actual heart-attack-preventative value of statins is pretty limited. And, as we have now learned, cholesterol does a great many important things—it is for precisely these reasons that the wholesale lowering of cholesterol is not a great idea. Armed with this information, you can probably make an educated guess as to the side effects of statins: sexual dysfunction (due to lowered sex hormones), muscle pain, weakness, fatigue, and memory and cognition problems.

The True Lurking Killers: Oxidation and Inflammation

The last few years has seen an absolute boom of antioxidant products hitting the market, and with very good reason. Antioxidants (as the name would imply) help to prevent oxidation, and oxidation is a true villain in this scenario. Oxidation leads to inflammation, and inflammation is what kills.

As Peter Attia noted earlier, the only “bad outcome” occurs when an oxidized LDL-B particle invades the endothelium, the one-cell-thick inner wall of the artery.

First, a word on oxidation: molecules contain multiple pairs of electrons—when one pair breaks apart, it creates an unpaired electron that needs to pair back up. This is what’s called a free radical molecule. This free radical seeks out other paired molecules and takes an electron, breaking the molecular bond. Then both molecules that were formerly paired and stable become free radicals, triggering a destructive and exponential chain reaction that can only be stopped by antioxidants. This is what we call oxidative stress.

Antioxidants can stop the oxidation process (and thus oxidative stress) by donating a molecule to the free radical, in essence shutting down the insurrection. If free radicals are an armed anarchist militia, antioxidants are a peacekeeping force.

It’s beyond the scope to get into a full discussion of inflammation here, but this much needs to be said. Acute inflammation is the body’s way of fighting off infection, and is a good thing. Chronic inflammation is when our immune systems launch a full attack on an area undergoing oxidative stress.

The Great Cholesterol Myth explains inflammation in the arterial wall. To paraphrase: When an oxidized (damaged) LDL particle sticks in the arterial wall, the body sends in the artillery, and the response creates inflammation. The lining of the arterial wall will secrete “adhesion molecules” that help to anchor the fighting force in place. The monocytes dispatched to the scene of the crime morph into “macrophages” (Latin for big eater) that eat the damaged LDL particles and other junk. They eat until the invader is gone, but it isn’t an outside invader: it’s damaged LDL and that damage is caused by sugar, starches, and oxidation. More damaged LDL arrives, the cycle continues.

Macrophages continue feasting, burst, and release new toxins, known as a “fatty streak.” The body tries to contain this, and builds a wall around it, creating scarring on the arterial lining. If the cycle continues, the fatty streak turns into plaque, the thing we have all (deservedly) come to fear.

If the inflammation continues unchecked, macrophages turn into a slimy “lipid core” that is released into the bloodstream. The body responds to this by forming a blood clot around it to keep it contained—a good thing. The downside to blood clots is that they can show up in places they are not supposed to, leading to strokes and heart attacks, among other things.

So it turns out cholesterol isn’t really to blame for all this mess—damaged cholesterol is. And that damage is the result of oxidation and glycation, in which high blood sugar changes LDL cholesterol. Of course, the other big factor in play is the triglyceride to HDL ratio, which is also dramatically worsened through eating sugar and being sedentary.

True Risk Prevention

The Nurses’ Health Study, conducted by Harvard, followed over 120,000 nurses since 1976. It is one of the largest, longest-running, and most well-respected studies tracking heart disease, strokes, cognitive function, and cancer among other things.

It found that smoking, excessive alcohol consumption, obesity, lack of exercise, and a diet high in trans fats and refined carbs were the main risk factors for coronary heart disease and strokes. (A “Mediterranean diet” high in fish, olive oil, nuts, and healthy fiber was a strong plus.)

When the risk factors were tallied up objectively, total cholesterol didn’t make the list. I think there’s a lesson there.

 

Further reading: To explore this topic further, check out The Great Cholesterol Myth by Jonny Bowden and Stephen Sinatra.